U.S. patent number 8,267,883 [Application Number 12/817,585] was granted by the patent office on 2012-09-18 for photocatalytic implant having a sensor.
This patent grant is currently assigned to DePuy Spine, Inc.. Invention is credited to Mohamed Attawia, Timothy Beardsley, Thomas M. DiMauro, John Daniel Malone, Hassan Serhan, Jeffrey K. Sutton.
United States Patent |
8,267,883 |
DiMauro , et al. |
September 18, 2012 |
Photocatalytic implant having a sensor
Abstract
An implant comprises a photocatalytic layer on at least one
surface and is adapted to act as a sensor. In some embodiments, the
photocatalytic layer is a semiconductor oxide that is doped.
According to some embodiments, the implant comprises a wave guide.
According to some embodiments the implant comprises a light port.
According to some embodiments, the implant comprises a reflective
material on a surface of the waveguide. According to some
embodiments the implant comprises a composite material comprising a
first material that has a transmissivity when exposed to a
predetermined wavelength of light and a second material that has
photocatalytic activity when exposed to the predetermined
wavelength of light. According to some embodiments the implant
comprises a light source adapted to irradiate the photocatalytic
surface.
Inventors: |
DiMauro; Thomas M. (Raynham,
MA), Sutton; Jeffrey K. (Raynham, MA), Attawia;
Mohamed (Holmdel, NJ), Serhan; Hassan (Raynham, MA),
Malone; John Daniel (Raynham, MA), Beardsley; Timothy
(Raynham, MA) |
Assignee: |
DePuy Spine, Inc. (Raynham,
MA)
|
Family
ID: |
43307009 |
Appl.
No.: |
12/817,585 |
Filed: |
June 17, 2010 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20100317948 A1 |
Dec 16, 2010 |
|
Related U.S. Patent Documents
|
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
10774105 |
Feb 6, 2004 |
7744555 |
|
|
|
Current U.S.
Class: |
604/8; 422/122;
424/423; 604/501; 604/20 |
Current CPC
Class: |
A61L
31/146 (20130101); A61L 27/06 (20130101); A61L
27/56 (20130101); A61F 2/30767 (20130101); A61L
31/124 (20130101); A61N 5/0624 (20130101); A61L
27/427 (20130101); A61L 31/022 (20130101); A61B
17/866 (20130101); A61F 2002/443 (20130101); A61M
5/158 (20130101); A61F 2/38 (20130101); A61F
2/36 (20130101); A61F 2002/3625 (20130101); A61F
2002/3611 (20130101); A61F 2/4455 (20130101); A61F
2002/30663 (20130101); A61F 2/34 (20130101); A61F
2/3662 (20130101); B01J 35/004 (20130101); A61F
2310/00023 (20130101); A61F 2310/0061 (20130101); A61N
2005/0651 (20130101); A61N 5/0601 (20130101); A61F
2002/30929 (20130101); A61F 2310/00616 (20130101); A61N
2005/0661 (20130101); A61F 2310/00604 (20130101); A61F
2/3094 (20130101) |
Current International
Class: |
A61M
5/00 (20060101); A61N 1/30 (20060101); A61F
2/00 (20060101); A62B 7/08 (20060101) |
Field of
Search: |
;604/8,20,501,174,180,96.01,890.1 ;422/139,122 ;424/423 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
10277144 |
|
Oct 1998 |
|
JP |
|
2002113108 |
|
Apr 2002 |
|
JP |
|
2003260126 |
|
Sep 2003 |
|
JP |
|
Other References
Akin, "Preparation and analysis of macroporous Ti02 films on Ti
surfces for bone-tissue implants", J. Biomed. Mat. Res., 2001, pp.
588-596, vol. 57. cited by other .
Anpo, "Utilization of Ti02 photocatalysts in green chemistry", Pure
Appl. Chem., 2000, pp. 1265-1270, vol. 72(7). cited by other .
Kaplan, "Biomaterial-induced alterations of neutrophil superoxide
production", J. Biomed. Mat. Res., 1992, pp. 1039-1051, vol. 26.
cited by other .
Ohko, "Self-sterilizing and self-cleaning of silicone catheters
coated with Ti02 photocatalyst thin films--A preclinical work", J.
Bio. Med. Mat. Res., 2001, pp. 97-101 vol. 58. cited by other .
Ramires, "The influence of titania/hydroxyapatite composite
coatings on in vitro osteoblasts behavior", Biomaterials, Jun.
2001, pp. 1467-1474, vol. 22(12). cited by other .
Shah, "Study of Nd3+, Pd2+, Pt4+ and Fe3+ dopant effect on
photoreactivity of Ti02 nanoparticles", PNAS, Apr. 30, 2002, pp.
6482-6486, vol. 99(S2). cited by other .
Shanbhag, "Decreased neutrophil respiratory burst on exposure to
cobalt-chrome alloy and polystyrene in vitro", J Biomed Mar. Res,
1992, pp. 185-195, vol. 26. cited by other .
Stutzman, "GaN-based heterostructures for sensor applications",
Diamond and Related Materials, 2002, pp. 886-891, vol. 11. cited by
other .
Trampuz, "Molecular and antibiofilm approaches to prosthetic joint
infection", Clin Orthop., 2003, pp. 69-88. vol. 414. cited by other
.
Trepanier, "Effect of modification of oxide layer on NiTi stent
corrosion resistance", J. Biomed. Mat. Res., 1998, pp. 433-440,
vol. 43. cited by other .
Wainright, "Photodynamic antimicrobial chemotherapy PACT", J
Antimicrobial Chemotherapy, 1998, pp. 13-28, vol. 42. cited by
other .
Wolfrum, "Photocatalytic oxidation of bacteria, bacterial and
fungal spores, and model biofilm components to carbon dioxide on
titaniu, dioxide-coated surfaces", ES&T, 2002, pp. 3412-3419,
vol. 36. cited by other .
Yin, "Preparation of nitrogen-dopes titania with high visible light
induced photocatalytic activity by mechanochemical reaction of
titania and hexamethylenetetramine", Mater. Chem., 2003, pp.
2996-3001, vol. 31(12). cited by other .
Zeina, "Killing of cutaneous microbial species by photodynamic
therapy", Br. J. Dermatol., 2001, pp. 274-278, vol. 144(2). cited
by other .
Zeina, "Cytotoxic effects of antimicrobial photodynamic therapy on
keratinocytes in vitro", B. J. Dermatol. 2002, pp. 568-573, vol.
146. cited by other.
|
Primary Examiner: Stephens; Jacqueline F.
Parent Case Text
CONTINUING DATA
This patent application is a continuation-in-part of co-pending
U.S. Ser. No. 10/774,105, filed Feb. 6, 2004, entitled "Implant
having a Photocatalytic Unit" (DiMauro et al).
Claims
We claim:
1. A medical implant comprising: a) photocatalytic surface, and b)
a light source adapted to irradiate the photocatalytic surface with
light in an amount sufficient to activate photocatalysis thereon,
wherein the implant is adapted to act as a sensor.
2. The implant of claim 1 wherein the sensor comprises the
photocatalytic surface.
3. The implant of claim 1 wherein the sensor comprises the light
source.
4. The implant of claim 3 wherein the sensor comprises a detection
system.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a prosthetic implant having a
photocatalytic layer adapted to fight periprosthetic infection.
2. Description of the Related Art
It is well known that infections occur in about 1% to about 5% of
all primary arthroplasties, and that "the economic impact, the
morbidity, and the emotional trauma of prosthetic joint infection
is immense and devastating to the patient and society". Trampuz et
al., Clin. Orthop., (414), 2003 pp. 69-88. It is believed that a
majority of these infections occur via transmission from microbes
upon the surgical gloves, the patient's skin, implants or
instruments. Unlike routine systemic infections, infections
associated with implants ("periprosthetic infections") are
particularly troublesome.
It has been reported that certain biomaterials cause an abnormal
and inferior immune response. In short, a portion of the immune
response is provided by the release of superoxide ions, such as
hydroxyl radicals, that are lethal to microbes. However, when a
periprosthetic infection occurs, it has been reported that
biomaterials such as cobalt chrome alloys cause abnormal neutrophil
activity, resulting in an inferior non-productive immune response.
Shanbhag, J. Biomed. Mar. Res., Vol. 26, 185-95, 1992.
It appears that the presence of the implant surface helps the
microbes survive both the immune response and antibiotic treatment.
In particular, microbes of concern attach to the implant surface
and form a polymer-like glaze (or "biofilm") between themselves and
the local environment. This biofilm acts as an effective barrier to
both neutrophils and antibiotics.
Although the periprosthetic infection itself is a primary concern
for the patient, it is also known that the immune response
triggered by the body to fight the infection also results in bone
loss. In particular, the increased phagocyte concentration also
increases the local concentration of tumor necrosis factor
(TNF-.alpha.). The TNF-.alpha. concentration in turn upregulates
the local level of osteoclasts. These increased osteoclast
concentration uncouples the normal balance in bone metabolism,
thereby leading to localized bone loss. This localized bone loss
may result in the loosening of the implant, thereby necessitating
its removal.
U.S. Pat. No. 6,503,507 ("Allen") discloses the use of a
light-activated composition that produces singlet oxygen. Allen
discloses that the singlet oxygen produced therefrom is effective
in killing bacteria. U.S. Pat. No. 6,527,759 ("Tachibana")
discloses the use of light activated drugs that produce singlet
oxygen.
Implant Sciences Corp. has promoted a surface treatment for
percutaneous medical devices that prevents the growth of bacteria
by employing the germ-fighting properties of silver coatings. U.S.
Pat. No. 6,592,888 ("Jensen") discloses the use of metallic
compounds in wound dressings to produce anti-microbial effects.
U.S. Pat. No. 6,605,751 ("Gibbins") discloses the use of silver
containing anti-microbial hydrophilic compositions. US Patent
Application 20030204229A1 ("Stokes") discloses the use of a
polymeric casing containing cations as biologically active agents
to be used on medical implants and devices.
Ohko, J. Biomed. Mat. Res. (Appl Biomat) 58: 97-101, 2001 reports
coating titania upon silicone catheters and medical tubes, and
illuminating those tubes with UV light. Ohko further reported the
bactericidal effect of the subsequent photocatalysis on E. coli
cells. However, Ohko states that TiO.sub.2 is toxic under
illumination, and that because the part of the TiO.sub.2 coating
buried in the patient's body can not be illuminated, the coating
should not be harmful to the body. Therefore, it appears that Ohko
discourages the in vivo irradiation of titania.
US Published Patent Application 2003/0125679 ("Kubota") discloses a
medical tube comprising an elastomer and a photocatalyst layer,
wherein the tube has excellent antibacterial activity.
Trepanier, J. Biomed. Mat. Res. (Appl Biomat) 43, 433-440 (1998)
reports providing an oxide layer of less than 1000 angstroms upon a
NiTi cardiovascular stent.
SUMMARY OF THE INVENTION
According to some embodiments of the invention, an implant
comprises a surface adapted for attachment to bone, with the
surface comprising a semiconductor oxide. According to some
embodiments of the invention, the semiconductor oxide has an
average pore size of no more than 10 um and a thickness of at least
0.2 um.
According to some embodiments of the invention, an implant
comprises a base material having an outer surface, a wave guide,
and a photocatalytic layer. The wave guide comprises an inner
surface and an outer surface, wherein the inner surface of the wave
guide is disposed adjacent the outer surface of the base material.
The photocatalytic layer comprises a semiconductor oxide having an
inner surface disposed adjacent the outer surface of the wave
guide.
According to some embodiments of the invention, an implant
comprises a base material having an outer surface, a waveguide and
a light port. The wave guide comprises an inner surface disposed
adjacent the outer surface of the base material and the light is
port coupled to the waveguide and adapted to receiving a light
signal.
According to some embodiments of the invention, an implant
comprises a photocatalytic layer comprising a semiconductor oxide
having an outer surface that is doped.
According to some embodiments of the invention, an implant
comprising a semiconductor oxide having an outer surface that has a
maximum light absorption wavelength of at least 400 nm.
According to some embodiments of the invention, an implant
comprises a base material having an outer surface, a semiconductor
oxide layer and a reflective material. The semiconductor oxide
comprises an inner surface and an outer surface, wherein the inner
surface of the semiconductor oxide is disposed adjacent the outer
surface of the base material, and the reflective material has inner
surface that is disposed upon the outer surface of the
semiconductor oxide.
According to some embodiments of the invention, an implant
comprises a composite material comprising a first material and a
second material. The first material has a transmissivity of at
least 50% when exposed to a predetermined wavelength of light; and
the second material has photocatalytic activity when exposed to the
predetermined wavelength of light.
According to some embodiments of the invention, a biomedical
implant comprises a photocatalytic surface and a light source
adapted to irradiate the photocatalytic surface. The light source
and the photocatalytic surface are configured such that the
irradiation of the photocatalytic surface with the light source
produces a photocatalytic effect.
According to some embodiments of the invention, a photocatalytic
system comprises an implant having a photocatalytic surface and an
external light source adapted to irradiate the photocatalytic
surface of the implant.
According to some embodiments of the invention, a method of
treating a prosthetic implant, comprising the acts of implanting an
implant having a photocatalytic surface into a patient, and
irradiating the photocatalytic surface to produce a photocatalytic
effect within the patient.
According to some embodiments of the invention, a prosthetic
vertebral endplate comprises a first surface, a second surface, a
body portion and an oxide surface. The first surface is adapted to
mate with a vertebral body. The second surface comprises an
articulation surface suitable for supporting articulation motion.
The body portion connects the first and second surfaces, and the
oxide surface is a titanium dioxide (TiO2) surface.
According to some embodiments of the invention, a prosthetic
vertebral endplate comprises a first surface, a second surface and
a functional unit. The first surface is adapted to mate with a
vertebral body. The second surface comprises a substantially
central articulation surface suitable for supporting articulation
motion, with the articulation surface defining first and second
lateral portions of the vertebral endplate. The functional unit can
be located adjacent one of the first and second lateral portions of
the endplate.
According to some embodiments of the invention, a method of
performing a procedure upon a patient, comprising the acts of
providing a cylinder comprising an outer surface having a
photocatalytic layer, advancing the cylinder through a tissue of
the patient, and, irradiating the photocatalytic layer of the
cylinder so that at least a portion of the irradiated
photocatalytic layer is in contact with the tissue.
According to some embodiments of the invention, a cylinder for
penetrating a tissue of a patient, comprises a distal end portion
adapted to penetrate tissue, an elongated intermediate portion, a
proximal portion, a base material forming an outer surface; and a
photocatalytic layer disposed upon at least a portion of the outer
surface.
According to some embodiments of the invention, a sterilization
system comprises a cylinder for penetrating a tissue of a patient
and a light transmission device coupled to the proximal end portion
of the cylinder. The cylinder comprises a distal end portion
adapted to penetrate tissue, an elongated intermediate portion, a
proximal portion, a base material forming an outer surface, and a
photocatalytic layer disposed upon at least a portion of the outer
surface of the base material.
According to some embodiments of the invention, a method of
disinfecting skin of a patient, comprises the acts of providing a
substrate comprising a photocatalytic layer, contacting the
photocatalytic layer with a liquid comprising oxygen, irradiating
the photocatalytic layer of the substrate in contact with the
liquid to produce reactive oxygen species, and contacting the
reactive oxygen species with the skin of the patient.
According to some embodiments of the invention, a shunt device
comprises a structural component housed within a tubing. The tubing
comprises an outer tube having an outer wall and an inner wall, a
photocatalytic layer attached to the inner wall of the outer tube,
and a light port.
According to some embodiments of the invention, a shunt device
comprises a structural component housed within a tubing. The
structural component comprises a baseplate having a first surface,
and a photocatalytic layer disposed upon a first portion of the
first surface of the baseplate.
According to some embodiments of the invention, a method of
performing a procedure upon a patient comprises the acts of
providing a shunt comprising a structural component housed within a
tubing having an inner surface, wherein at least one of the
structural component and the inner surface of the tubing has a
photocatalytic layer disposed thereon, implanting the shunt in the
patient, and irradiating the photocatalytic layer.
According to some embodiments of the invention, an infusion set
comprises a needle housing, a mounting pad, and a transcutaneous
cannula. The needle housing has a proximal port, a distal port and
a base surface. The mounting pad is coupled to the base surface of
the needle housing. The transcutaneous cannula has a proximal end
connected to the distal port of the needle housing and a distal
end. The transcutaneous cannula also has an ex vivo portion and an
in-dwelling portion, and comprises an inner silicon tube having an
outer wall and an inner wall, and an outer photocatalytic layer
attached to the outer wall of the silicon tube.
DESCRIPTION OF THE DRAWINGS
The accompanying drawings, are not intended to be drawn to scale.
In the drawings, each identical or nearly identical component that
is illustrated in various figures is represented by a like numeral.
For purposes of clarity, not every component may be labeled in
every drawing. In the drawings:
FIG. 1 is a cross-section of a surface portion of a titanium
implant, wherein the surface has been oxidized to produce a thick
titania layer.
FIG. 2 is a cross-section of a surface portion of a titanium
implant having an oxidized surface, wherein the surface has been
further bombarded with a dopant.
FIG. 3 is a cross-section of titanium alloy (Ti4Al6V) surface of an
implant, wherein the surface has been further oxidized.
FIG. 4 is a cross-section of a portion of an implant having an
intermediate waveguide layer and an upper photocatalytic layer.
FIG. 5 is a cross-section of a portion of an implant having a
composite coating comprising a waveguide and a photocatalytic
material.
FIG. 6 is a cross-section of a portion of an implant having a
porous composite coating comprising a waveguide and a
photocatalytic material.
FIG. 7 is a cross section of a needle containing a fiber optic
cable.
FIG. 8 is a cross section of a portion of an implant having a port
for connecting a fiber optic.
FIG. 9 is a cross-section of a portion of an implant having a
waveguide layer, a photocatalytic layer, and an outer reflective
layer.
FIG. 10 is an implant having a lower waveguide layer, an
intermediate reflective layer, and an outer porous photocatalytic
layer.
FIG. 11 is a cross-section of a photocatalytic oxidation ("PCO")
unit, wherein the light source is external to the body.
FIG. 12 is a cross-section of telemetry-powered PCO unit.
FIG. 13 is a schematic of an implant of the present invention.
FIG. 14 is a cross-section of an implant having an apparatus for
delivering fluids.
FIG. 15 is a cross-section of a hip implant of the present
invention.
FIG. 16 is a cross-section of a knee implant of the present
invention.
FIG. 17 is a cross-section of a screw implant of the present
invention.
FIG. 18 is a cross-section of an Intervertebral Fusion implant of
the present invention.
FIG. 19 is a cross-section of an intervertebral motion disc implant
of the present invention.
FIG. 20 is a cross-section of a spinal deformity correction unit of
the present invention.
FIG. 21 is a cross-section of a device of the present invention
wherein both the light source and an antenna are provided on the
outer surface of the implant at the implant-bone interface.
FIG. 22 is a cross-section of a device of the present invention
wherein both the light source and the antenna are provided on an
inner surface of the implant.
FIG. 23 is a cross-section of a device of the present invention
wherein both the light source and the photocatalytic layer are
provided on the rim of the implant.
FIG. 24 is a cross-section of a device of the present invention
wherein the light source is provided on an outer surface of the
implant at the implant-bone interface and the antenna is provided
on an inner surface.
FIG. 25 is a cross-section of a device of the present invention
wherein a titanium-containing surface of the implant is oxidized to
produce a photocatalytic surface.
FIG. 26 is a cross-section of a device of the present invention
wherein a porous scaffold containing titanium dioxide is applied to
a surface of the implant to produce a photocatalytic surface.
FIG. 27 is a cross-section of a device of the present invention
wherein a wave guide is placed adjacent an LED to diffuse the light
from its source.
FIG. 28 is a cross-section of a device of the present invention
wherein the implant has a porous scaffold comprising a UV
transmissible material and a semiconductor material.
FIG. 29 is a prior art representation of a periprosthetic
infection.
DETAILED DESCRIPTION OF THE INVENTION
This invention is not limited in its application to the details of
construction and the arrangement of components set forth in the
following description or illustrated in the drawings. The invention
is capable of other embodiments and of being practiced or of being
carried out in various ways. Also, the phraseology and terminology
used herein is for the purpose of description and should not be
regarded as limiting. The use of "including," "comprising," or
"having," "containing", "involving", and variations thereof herein,
is meant to encompass the items listed thereafter and equivalents
thereof as well as additional items.
For the purposes of the present invention, "titanium dioxide" is
also referred to as titania and TiO.sub.2. A "UV light source"
includes any light source emitting light having a maximum energy
wavelength of between about 0.1 nm and about 380 nm. A "UVC light
source" includes any light source emitting light having a maximum
energy wavelength of between about 0.1 nm and less than 290 nm. A
"UVB light source" includes any light source emitting light having
a maximum energy wavelength of between 290 nm and less than 320 nm.
A "UVA light source"includes any light source emitting light having
a maximum energy wavelength of between 320 nm and less than 380 nm.
A "visible light source" includes any light source emitting light
having a maximum energy wavelength of between 380 nm and less than
780 nm. An "infrared light source" includes any light source
emitting light having a maximum energy wavelength of between 780 nm
and less than one million nm.
A "reactive oxygen species" includes, for example, hydrogen
peroxide, hydroxyl radicals, superoxide ion, and singlet oxygen and
is also referred to as "ROS".
As will be discussed in detail infra, one aspect of the invention
comprises a photocatalytic unit (PCO) comprising a photocatalytic
layer. For example, some embodiments of the photocatalytic unit
comprise an implant device having a photocatalytic layer. The PCO
may also comprise a light source. Upon illumination of the
photocatalytic layer with light from the light source, the
photocatalytic layer locally generates a plurality of reactive
oxygen species, such as singlet oxygen. The reactive oxygen species
(ROS) produced by this system are potent anti-microbial agents
capable of destroying not only local microbes but also
periprosthetic biofilms. However, because of the potency of the
ROS, the ROS typically react very quickly with surrounding organic
material and so have a very local effect.
According to some embodiments, the photocatalytic layer comprises a
semiconductor material, and is can be a metal oxide, such as
titanium dioxide. Titanium dioxide has been shown to have
photocatalytic activity for generating ROS.
In some embodiments, the implant device is illuminated with an
external source of light. For example, the light source could be
the operating room lights. The light source could also be an
external light box in which the device is placed just prior to
implantation. In other embodiments, a suitable fiber-optic device
is connected to the external light source and passed through the
patient's skin to connect with the implanted device.
In some embodiments, the photocatalytic layer of the implant device
is doped to enhance or prolong the photocatalytic effect. Some
exemplary dopants include, but are not limited to, metal alloys or
ions of chromium and/or vanadium; phosphorescent compounds,
ligands, or ions; organic compounds containing oxygen-rich chemical
species such as peroxides, superoxides, acids, esters, ketones,
aldehydes, ethers, epoxides, and lactones; and organic compounds
containing conjugated systems, such as photostabilizers and
dyes.
Alternatively or additionally according to some embodiments, the
implant device could be illuminated after implantation and all
surgical manipulations have been performed. Such post-implantation
illumination could be performed just prior to surgical closure, for
example, or after some period of time has elapsed by a percutaneous
access approach using a fiber-optic surgical delivery device.
In some embodiments, a light port is incorporated into the implant
device to provide efficient delivery and coupling of the light
energy to the photocatalytic layer. The light port can include a
self-sealing gland to prevent contamination and occlusion of the
light receiving port, thereby providing efficient energy transfer.
Additionally, the light port could include a radiopaque marker,
e.g. a tapered cylinder or other geometry, to allow the surgeon to
efficiently direct a percutaneous needle with a fiber optic to the
desired site under fluoroscopic guidance.
According to some embodiments, the implant device could comprise a
waveguide layer to deliver light energy to the photocatalytic
layer. The waveguide layer could, for example, be located
underneath the photocatalytic layer, e.g. between the
photocatalytic layer and the base material of the implant. It may
be desirable for the waveguide layer to be of a different material
than the photocatalytic layer to allow efficient energy transfer.
For example, an undoped titanium oxide layer uses light having a
wavelength of less than 380 nm to induce the photocatalytic effect.
However, titanium oxide is moderately to strongly light absorbing
at wavelengths below .about.450 nm, and so would not function
efficiently as a waveguide to propagate the light to all areas of
the implant device. Accordingly, the use of a UV transmissive
material as the waveguide layer, such as silicon oxide, aluminum
oxide, or other materials with low absorption at the relevant
wavelengths, would allow the light to reach regions distant from
the light port or entry point.
According to some embodiments of an implant device, there can be
provided a partially reflecting layer on at least one surface of
the waveguide layer that would enhance the transmission of light
energy within the waveguide. For example, it may be desirable to
have the surface adjacent to the photocatalytic layer be partially
reflective or transmissive, with all other surfaces of the
waveguide totally reflective. In some embodiments, silver metal is
used as the reflective layer, having known desirable optically
reflective properties as well as known anti-microbial properties.
It is to be appreciated that alternative reflective materials such
as aluminum or gold metal can also be used.
According to some embodiments, dopants as described above, and
particularly metal ions, are provide to the photocatalytic layer
which comprises titanium oxide so as to modify the band gap energy
of the titanium oxide layer, such that visible light greater than
380 nm can be used to effectively induce the photocatalytic
activity. For such embodiments, the photocatalytic layer could also
act as the waveguide layer, and a partially reflective silver
coating could be provided to enhance the internal reflection of the
light to efficiently spread the light energy throughout the layer.
As discussed herein, the selection of silver for the reflective
layer also provides additional anti-microbial activity.
In some embodiments involving, for example, orthopedic implants,
the implant can incorporate a porous layer on surfaces in direct
contact with bone to facilitate osseointegration. These porous
layers can be fabricated, for example, from titanium using a
plasma-spray method, generating pore sizes ranging from 10 .mu.m to
.about.500 .mu.m, with .about.200-300 .mu.m being an exemplary
useful range. According to some embodiments, the porous network can
also deliver therapeutic fluids, e.g. antibiotics, hormones, growth
factors, BMP's, anti-inflammatory agents, etc. Since titanium
readily forms an oxide on its surface, this porous layer may be
utilized as a waveguide and photocatalytic layer, as well as a
fluid channel to deliver therapeutic fluids to the surfaces of the
device. For example, the delivery of fluid to this layer may be
achieved by the use of the light port as described above, and using
a standard hypodermic needle (e.g., without a fiber optic), to
deliver fluid to the light port instead of or in addition to
light.
According to some embodiments, a coating or layer of resorbable
material can be provided on the surface of the device to partially
or completely seal the surface to enhance the delivery of fluid
throughout the device, thus preventing delivered fluid from
immediately leaking out of the delivery site and not spreading
uniformly throughout the porous layer. Such a coating or layer may
be made of silver metal, thereby generating the desirable
properties of anti-microbial activity and also reflectivity for the
waveguide/photocatalytic aspects of the layer.
According to one aspect of the invention, it is believed that the
photocatalytic unit of the present invention works to effectively
fight a periprosthetic infection (PPI) as is disclosed herein.
It is known that neutrophils play a critical role in fighting
infection in the body. It is believed that when the body recognizes
a foreign body, such as an implant, signaling from the immune
system calls neutrophils to the implant location. The neutrophils
proceed to emit a number of infection-fighting molecules, including
reactive oxygen species (ROS), such as superoxide ion. It is
believed that the ROS, and the superoxide ion in particular, cause
the death of the pathogenic bacteria by penetrating the cells wall
of the bacteria.
Kaplan et al., J. Biomed. Mat. Res., 26, 1039-51 (1992)
investigated the role played by neutrophils in periprosthetic
infection (PPI) and found that the neutrophils prematurely emit
their infection-fighting compounds and, when the infection is
sustained, appear to exhaust their capability of manufacturing more
of these infection fighting compounds. Accordingly, it appears that
the body response to PPI includes a dose of apparently potent
compounds, but that dose is not sustained. When the release period
ends, the body does not adequately respond to the PPI.
In sum, the typical immune response of the body to an infection
involves the release of superoxide ions by local neutrophils in
amounts that are lethal to the local bacteria, and periprosthetic
infection often arises due to the implant's interference with this
natural activity.
When the semiconductor element of the PCO of the present invention
is properly irradiated by the UV light source, it is believed that
reactive oxygen species (ROS) are produced at the semiconductor
surface and enter the body fluid adjacent the photocatalytic
surface. These ROS include hydroxyl radicals (.OH), hydrogen
peroxide (H.sub.2O.sub.2), superoxide ion (.sup.-O.sub.2) and
singlet oxygen (O) and appear to be the same ROS naturally produced
by neutrophils in the natural immune response to PPI. However,
whereas the neutrophil response is limited both in magnitude and
duration, the PCO unit of the present invention can be tuned to
emit ROS in both a magnitude and for a duration deemed appropriate
for the extent of infection diagnosed by the clinician.
According to some embodiments, when an effective amount of light
irradiates the photocatalytic surface of the PCO of the present
invention, the sensitized surface can effectively catalyze both the
oxidation of water (to produce hydroxyl radicals .OH) and the
reduction of oxygen (to produce superoxide radicals .sup.-O.sub.2).
It is believed that PCO may also produce significant amounts of
hydrogen peroxide.
Accordingly, activation of the PCO unit disposed on an implant can
effectively produce and release the same molecular units naturally
released by the patient's full-strength immune system. Therefore,
it is believed that at least the superoxide radicals O.sub.2--
produced by the PCO unit effectively kill at least the free
floating bacteria that are not protected by a biofilm.
As stated above, it is believed that the PCO unit of some
embodiments of the present invention comprising a semiconductor
device, causes the production of hydrogen peroxide near or upon the
semiconductor surface. It is well known that hydrogen peroxide is
lethal to bacteria. In some embodiments, the PCO unit produces a
local concentration of hydrogen peroxide believed to be sufficient
to kill Staphylococcus epidermis. In some embodiments, the PCO unit
can be constructed and arranged to produce a local concentration of
hydrogen peroxide in the range typically produced by natural
neutrophils in response to an infection. In some embodiments, the
PCO unit can be constructed and arranged to produce a local
concentration of hydrogen peroxide believed to be sufficient to
oxidize a biofilm.
As stated above, the PCO unit of the present invention comprising a
semiconductor device can be constructed and arranged to cause the
production of superoxide ion upon the semiconductor surface. It is
well known that superoxide ion is lethal to bacteria. In some
embodiments, the PCO unit can be constructed and arranged to
produce a local concentration of superoxide ion believed to be
sufficient to kill Staphylococcus epidermis. In some embodiments,
the PCO unit can be constructed and arranged to produce a local
concentration of superoxide ion in the range typically produced by
natural neutrophils in response to an infection. In some
embodiments, the PCO unit can be constructed and arranged to
produce a local concentration of superoxide ion believed to be
sufficient to oxidize a biofilm.
As stated above, the PCO unit of some embodiments of the present
invention comprising a semiconductor device can be constructed and
arranged to cause the production of hydroxyl radicals upon the
semiconductor surface. It is well known that hydroxyl radicals are
particularly lethal to bacteria. In some embodiments, the PCO unit
can be constructed and arranged to produce a local concentration of
hydroxyl radicals believed to be sufficient to kill Staphylococcus
epidermis. In some embodiments, the PCO unit can be constructed and
arranged to produce a local concentration of hydroxyl radicals in
the range typically produced by natural neutrophils in response to
an infection. In some embodiments, the PCO unit can be constructed
and arranged to produce a local concentration of hydroxyl radicals
believed to be sufficient to oxidize a biofilm.
As stated above, it is believed that the PCO unit of some
embodiments of the present invention comprising a semiconductor
device, can be constructed and arranged to cause the production of
hydrogen peroxide upon the semiconductor surface. It is believed
that providing some embodiments of the PCO upon an implant surface
will produce singlet oxygen (.sup.1O.sub.2) through the following
mechanism:
According to Allen, in the presence of sufficient halide,
H.sub.2O.sub.2 is the rate limiting substrate for haloperoxidase
microbicidal action. Microbicidal activity is linked to
haloperoxidase generation of hypohalous acid:
##STR00001## and to the secondary generation of singlet molecular
oxygen (.sup.1O.sub.2):
HOX+H.sub.2O.sub.2.fwdarw..sup.1O.sub.2+H.sub.2O (2). Both HOX and
.sup.1O.sub.2 are antimicrobial reactants.
The present inventors have appreciated that the PCO can be
constructed and arranged to produce both superoxide ion and
hydrogen peroxide, and that typical human interstitial fluid
contains a substantial amount of salts and so has significant
amounts of Cl.sup.-, a halide ion. Therefore, it is reasonable to
conclude that the native halide ion present in the vicinity of the
implant and the PCO-generated hydrogen peroxide may react to
produce HOX, and this HOX will further react with another
H.sub.2O.sub.2 molecule to produce singlet oxygen.
It is well known that singlet oxygen is lethal to bacteria. In some
embodiments, the PCO unit can be constructed and arranged to
produce a local concentration of singlet oxygen believed to be
sufficient to kill free-floating microbes. In some embodiments, the
PCO unit can be constructed and arranged to produce a local
concentration of singlet oxygen in the range typically produced by
natural neutrophils in response to an infection. In some
embodiments, the PCO unit can be constructed and arranged to
produce a local concentration of singlet oxygen believed to be
sufficient to oxidize a biofilm.
Although it appears that singlet oxygen is a very potent
antibiotic, its extreme reactivity limits its sphere of influence.
In particular, it is believed that singlet oxygen has an average
lifetime on the order of milliseconds and a sphere of influence of
only about 0.2 microns. Therefore, the production of singlet oxygen
provides a comprehensive disinfecting response, but only very close
to the surface of the implant so that the nearby tissue is
essentially unaffected.
Moreover, the present inventors have further appreciated the role
played by chain reactions in ROS chemistry, and the need to insure
that such reactions are self-limiting. It is believed that, since
the production of singlet oxygen requires two hydrogen peroxide
molecules, the above-stated reactions can be well-controlled due to
the eventual depletion of hydrogen peroxide.
In addition, it has been recently reported by Wolfrum, ES& T,
2002, 36, 3412-19 that photocatalytic oxidation effectively
destroys biofilms. Wolfrum reported that the reactive oxygen
species produced by its PCO unit effectively oxidized each of a
phospholipid, a protein and a polysaccharide film. Since Wolfrum
further stated that these substance were selected to be models of
polymer-like biofilm, it is reasonable to conclude that such a PCO
can not only destroy the biofilm protecting the foreign microbes,
but in doing so it will expose the previously protected bacteria to
lethal amounts of both hydroxyl radicals (.OH) and superoxide
radicals O.sub.2--.
Some embodiments of the photocatalytic unit of the present
invention comprise a light source and a photocatalytic surface
comprising a semiconductor material to be irradiated by the light
source. It is believed that, upon irradiation with an effective
amount of UV light, the semiconductor material can be provided in
an amount sufficient in the photocatalytic surface to produce a
sufficient amount of holes and electrons. The holes catalyze the
oxidation of water, thereby producing hydroxyl radicals .OH. The
electrons catalyze the reduction of oxygen, thereby producing
superoxide radicals O.sub.2--.
Accordingly, the semiconductor material according to some
embodiments comprises a solid catalyst comprising a transition
element, and according to some embodiments is selected from the
group consisting of titanium dioxide and ferric oxide. According to
some embodiments, it comprises titanium dioxide. In some
embodiments, the semiconductor is Degussa P25, available from
DeGussa.
In some embodiments, the photocatalytic surface is produced by
layering (for example by sonication) a powder comprising the
semiconductor material upon a surface capable of being irradiated
by the light source.
Now referring to FIG. 1, in some embodiments, there is provided an
implant 1 of the present invention, wherein a photocatalytic layer
5 is produced by oxidizing a base material 3 comprising titanium,
thereby producing a photocatalytic titania layer. According to some
embodiments, the photocatalytic titania layer has a thickness TH of
at least 0.2 um. Since many implants are made of titanium or
titanium alloys, the photocatalytic surface may be easily produced
by simply oxidizing a titanium surface on a portion of a
titanium-containing implant. According to some embodiments, the
oxidized surface resides in a non-load bearing portion of the
implant.
In some embodiments, since titania at least partially transmits UV
light, the thickness of the oxidized layer may be selected to be
sufficiently thick so as to also act as a waveguide. Therefore, in
some embodiments, the photocatalytic surface has a thickness of
between about 0.5 um and about 1.5 um, and preferably between about
0.8 and 1.2 um.
In some embodiments, the photocatalytic surface is produced by
providing sintered TiO.sub.2 beads upon an implant surface. In some
embodiments to be discussed infra, the TiO.sub.2 beads can be
sintered onto an implant-bone interface to create a porous scaffold
suitable for bony in-growth. For such arrangements, the porous
scaffold comprising the semiconductor oxide provides desirable
qualities including disinfection capabilities (due to its
photocatalytic qualities) and bone ingrowth capabilities (due to
its porous scaffold).
Moreover, the porous scaffold of this embodiment can be configured
to provide a convenient reaction zone for the photocatalytic
process. The PCO unit can therefore be tuned to provide ROS
throughout the reaction zone, while avoiding the diffusion of ROS
outside the reaction zone.
Since photocatalysis is a surface phenomenon, the depth of the
photocatalytic surface need not be particularly great. Moreover, it
has been reported by Ohko, J. Biomed. Mat. Res. (Appl Biomat) 58:
97-101, 2001 that when TiO.sub.2 thin films produced by heat
treating exceed about 2 um, the layer begins to peel from its
substrate. Therefore, in some embodiments, the photocatalytic
surface has a thickness of between about 0.2 um and about 2 um.
However, it is to be appreciated that the thickness can be outside
of this range, for example, as discussed above, in some
embodiments, the thickness of the photocatalytic layer may be
configured so as to act as a waveguide.
According to some embodiments, the photocatalytic surface comprises
a semiconductor material. According to some embodiments, the
semiconductor material is selected from the transition elements of
the Periodic Table. According to some embodiments, the
semiconductor material is selected from the group consisting of
titanium dioxide and ferric oxide. According to some embodiments,
the semiconductor is titania. In some embodiments, the
semiconductor is Degussa P25.
In some embodiments, the photocatalytic surface consists
essentially of the semiconductor material. These embodiments have
the advantage of manufacturing simplicity. In other embodiments,
the photocatalytic surface can comprise a composite comprising at
least a semiconductor material. According to some embodiments, the
photocatalytic surface can comprise a titania film on a titanium
surface. For example, Akin, J. Biomed. Mat. Res. 57, 588-596, 2001,
discloses the preparation of macroporous titania films upon
titanium surfaces Akin's films were reported to be about 0.1 mm to
about 1 mm in thickness. Pore sizes were reported to be 0.5 um, 16
um and 50 um.
In some embodiments, the photocatalytic surface comprises a
composite of a semiconductor material and a material suitable for
providing a scaffold for bony ingrowth. In some embodiments, the
scaffold material comprises a calcium phosphate (CaP) containing
material. According to some embodiments, the CaP-containing
material is selected from the group consisting of tricalcium
phosphate (TCP) and hydroxapatite (HA). The literature has reported
that films comprising HA/TiO.sub.2 are highly suitable for the
formation of a porous scaffold suitable for bony ingrowth. See,
e.g., Ramires, Biomaterials 2001, June; 22(12); 1467-74.
In some embodiments, the photocatalytic surface comprises a
composite of a semiconductor material and a light-transmissible
material. According to some embodiments, the light transmissible
material is a UV-transmissible material. According to some
embodiments, the UV-transmissible material is selected from the
group consisting of alumina, sapphire and silica. Moreover,
according to some embodiments this composite is made into a porous
scaffold, wherein the porous scaffold contains islands of TiO.sub.2
interspersed throughout the porous scaffold. Because the UV light
is not absorbed by the UV-transmissible portion of the material,
the UV light is absorbed only by the titania interspersed
throughout the scaffold. The titania present adjacent an internal
scaffold surface then becomes photoactivated and produces ROS
throughout the scaffold.
Now referring to FIG. 2, in some embodiments, the implant comprises
a base material 3 overlain by a photocatalytic layer 7. In this
case, the photocatalytic layer 7 comprises a composite layer of a
semiconductor material 8 doped with a dopant 9 that reduces the
bandgap of the photocatalyst, thereby increasing the maximum
wavelength of light absorbed by the photocatalytic layer. In some
embodiments, the dopant is selected from the group consisting of
vanadium and chromium.
It has been reported by Anpo et al, Pure Appl. Chem. Vol. 72, (7),
2000, pp. 1265-70 that when a dopant selected from this group is
ion-implanted onto a titanium dioxide surface, the resulting
surface is substantially photocatalytically active when irradiated
with white light.
In some other embodiments, the dopant is nitrogen. It has been
reported by Lin, J. Mater. Chem., 2003, 13(12)2996-3001 that when
nitrogen is selected as the dopant, the resulting surface is
substantially photocatalytically active when irradiated with light
having either a 400 nm or a 550 nm wavelength.
In some other embodiments, the dopant is selected from the group
consisting of Nd.sup.+3, Pd.sup.+2, Pt.sup.+4 and Fe.sup.+3. It has
been reported by Shah, PNAS, Ap. 30, 2002, 99(S.2), pp. 6482-6 that
when one of these dopants is selected as the dopant, the resulting
surface may be substantially photocatalytically active when
irradiated with 450-460 nm light. Therefore, in some embodiments,
the photocatalytic surface comprises a composite of a semiconductor
material doped with a dopant that reduces the bandgap of the
photocatalyst, thereby increasing the median wavelength of light
absorbed by the photocatalytic layer to include wavelengths greater
than UV.
In some embodiments using a dopant, a titanium implant is oxidized
to produce a titania surface layer, and this titania layer is then
ion-bombarded with a dopant.
It is well known that there are many commercial Ti-based alloys
commonly used in the medical devices that contain vanadium. One
common example of such as alloy is Ti4Al6V alloy, which comprises
90 wt % titanium, about 4 wt % aluminum, and about 6 wt % vanadium
(TMD: check)[**INFO]. The present inventors believe that simple
oxidation of this commercial alloy results in a photocatalytic
layer comprising titania and vanadium. As noted above, this
photocatalytic layer has special utility in that it can be
activated by white light.
Now referring to FIG. 3, there is provided an implant having a
Ti4Al6V alloy base material 11 and an oxidized surface 13. The
oxidized surface is a photocatalytic layer comprising titania and
vanadium 15. In some embodiments, the photocatalytic layer
activated by white light has a thickness of at least 1 um.
Since periprosthetic infections often form a biofilm that envelops
a substantial portion of the surface of the implant, it is
appreciated that it would be highly desirable to photoirradiate
substantially an entire surface of the implant. However, it is
further appreciated that orthopedic implants often have irregularly
shaped surfaces that are not conductive to direct irradiation from
a single (or even multiple) point light source. Moreover, the
presence of light-absorbing tissue adjacent the photocatalytic
surface further complicates the comprehensive irradiation of a
surface of the implant.
Now referring to FIG. 4, accordingly, in some embodiments, the
photocatalytic unit of the implant further comprises a base
material 3, a photocatalytic layer 23, and an intermediate
waveguide 21 adapted to transmit light from a light source to
distant surface portions of the implant. According to some
embodiments, the waveguide comprises a material that is at least
partially transmissible to UV or white light. When such a waveguide
is provided adjacent the photocatalytic layer, the light
irradiating the waveguide can travel via the waveguide throughout
the surface of the photocatalytic layer. One advantage is that the
light transmissible material acts as a wave guide, so that the UV
light generated from the light source can spread laterally across
the surface of the implant and thereby irradiate the photocatalytic
layer from, for example, the back side.
In some embodiments, the wave guide 21 can be provided as a
discrete layer between the inner surface 22 of the photocatalytic
layer 23 and the outer surface 20 of the base material 3 implant
(as illustrated in FIG. 4). In such embodiments, the waveguide
layer can be easily deposited by CVD processes.
Now referring to FIG. 5, in other embodiments, the wave guide can
be provided as part of a composite layer 27 comprising the
semiconductor material 29 and a light-transmissible (for example,
UV-transmissible) material 25. With this arrangement, the composite
layers act as both a wave guide and a photocatalytic surface. In
some embodiments, the composite layer 27 comprises between about 10
vol % and 20 vol % semiconductor and between about 80 vol % and 90
vol % waveguide. In some embodiments of the composite layer 27, the
composite is essentially dense (e.g., no more than 10 vol %
porous), thereby providing strength.
Now referring to FIG. 6, in other embodiments, the implant
comprises a base material 3 having an outer surface 20, a wave
guide 21 contacting the outer surface of the base material, and a
composite layer 27 overlying the wave guide and comprising a UV
transmissible material 25, including a semiconductor material 29
and also having an open porosity 30. In some embodiments, the
composite layer has a porosity having an average pore size of
between about 50 um and about 1000 um. This composite layer (e.g.,
alumina-titania) can also act as a porous scaffold over the entire
surface, thereby providing an osteoconductive surface suitable for
bony ingrowth.
In some embodiments of this arrangement, the light transmissible
material is selected from the group consisting of a ceramic and a
polymer. In some embodiments, suitable UV-transmissible ceramics
include alumina, silica, CaF, titania and single crystal-sapphire.
In some embodiments, suitable light transmissible polymers can be
selected from the group consisting of polypropylene and
polyesters.
According to such embodiments of this arrangement, irradiation of
any surface of the waveguide may be sufficient for the waveguide to
propogate the light throughout the adjacent photocatalytic surface
and generate ROS over that entire photocatalytic layer. Although
comprehensive irradiation is easily accomplished when performed at
the time of surgery (when the implant is visible to the surgeon),
if anti-microbial therapy is desired at some future, post-operative
time, then, for example, a minimally invasive fiber optic device
may be used to deliver the light to the waveguide, where
irradiation of the entire surface of the waveguide or
photocatalytic surface may be more problematic.
Accordingly, and now referring to FIGS. 7 and 8, when a wave guide
is used in conjunction with an external light source and light is
to be transmitted to the wave guide via a fiber optic, it is
desirable to provide a light port coupled to the wave guide in
order to provide easy connection of the fiber optic to the wave
guide.
FIG. 7 discloses a distal portion of a delivery needle 41 adapted
to deliver a fiber optic 103 to the waveguide. The needle 41
comprises a barrel 42 defining a small bore lumen 43 and a distal
opening 45. The distal portion of the barrel forms a needle tip 47
suitable for penetrating an orthogonally-disposed seal (not shown).
In some embodiments, the delivery needle can also be adapted to
contain both a waveguide 49 and inner 51 and outer photocatalytic
surfaces 53, so that the needle itself can be photo-sterilized to
minimize introduction of bacteria into or drawing bacteria from the
implant site.
As shown in FIG. 7, the needle is adapted to house a fiber optic
cable 103 that is connected to a light source 101. Light is
generated by the light source, is transported through the fiber
optic cable, and is emitted from the distal end 105 of the fiber
optic cable.
Now referring to FIG. 8, there is provided an implant comprising: a
base material 3, a waveguide 21 overlying the base material, a
photocatalytic layer 23 overlying the waveguide, and a light port
61 communicating with the waveguide. The light port according to
some embodiments comprises a proximal receiving portion 63 adapted
to receive and secure the delivery needle and includes a
throughbore 65, an intermediate seal 67 sealing the throughbore,
and a distal barrel portion 69.
In FIG. 8, the proximal receiving portion of the light port
comprises an inner bore 65 having a distally tapering circumference
71. It may also have a radio-opaque portion (not shown) that helps
the surgeon find its location under fluoroscopy. The distally
tapering circumference of the proximal receiving portion helps
guide the needle, as illustrated and such as shown in detail in
FIG. 7, into the proximal receiving portion. The proximal receiving
portion may also have a securing device, such as a luer lock
portion (not shown) in order to secure the needle within the light
port. In some other embodiments, the securing device comprises a
threaded recess adapted to mate with a threaded male distal portion
of the delivery needle or fiber optic
One function of the intermediate seal 67 is to prevent tissue
ingress to the light-communicating surface of the optically
transmissible waveguide. One function of the distal bore portion 69
is to provide a space allowing for needle over-insertion, thereby
minimizing physical damage to the waveguide portion of the implant
by the inserted needle. Thus, the light port of FIG. 8 receives a
needle such as that of FIG. 7 to provide the light from light
source 101 to the waveguide layer 21 of the implant.
However, if a wave guide is merely disposed as an interlayer
between an implant surface and the photocatalytic surface, then
there is a possibility that light traveling within the wave guide
will simply exit the lateral ends of the wave guide and enter the
adjacent tissue. In order to prevent such occurrences and thereby
enhance the efficiency of the light source, in some embodiments of
the present invention, and now referring to FIG. 9, the implant can
be provided with a reflective surface 31 adjacent an edge of the
wave guide 21, such as the distal end of the waveguide (from the
end having the light receiving port). The disposition of the
reflective layer at a wave guide lateral edge prevents laterally
moving light from exiting the lateral edge of the wave guide, and
rather reflects this light back into the wave guide and ultimately
into the photocatalytic layer 27.
In other embodiments, the reflective coating 31 can also be placed
on the outer surface 28 of a porous photocatalytic layer 27 in
order to reflect light escaping from the photocatalytic layer and
to reflect the light back into the photocatalytic layer.
In some embodiments thereof, the reflective surface comprises a
metal-containing layer, for example, coated upon a portion of the
waveguide or photocatalytic surface. The metal-containing layer may
be for example a pure metal, a metal alloy, or even a metal oxide
having a lower refractive index than the photocatalytic layer. In
some embodiments, the metallic coating is selected from the group
of metals consisting of silver and titanium. In some embodiments,
silver is used in order to take advantage of its antimicrobial
effect.
In some embodiments, the reflective surface comprises a multi-layer
structure designed to create a reflection within the waveguide
layer to better distribute light to the photcatalytic layer. For
example, and now referring to FIG. 10, it may be desirable to use a
multi-layer structure including, for example a visible light
transmissive titania as the waveguide, and an external layer of for
example vanadium-doped titania as the photocatalytic surface. In
particular, FIG. 10 illustrates an implant comprising base implant
material 3, a wave guide layer (such as pure titania) 21 overlying
the base material, a partially reflective layer 32 (such as Ti, Ag,
V or Cr) overlying the waveguide layer that partially reflects the
light within the waveguide to more evenly distribute the light to
the photcatalytic layer, and a white light-absorbing photocatalytic
outer layer 7 (for example, a vanadium-doped porous titania
layer).
With such embodiments, when irradiated by white light, the
waveguide layer may not generate any significant ROS (for example,
the pure titania bandgap would be too high for light having a
wavelength greater than 380 nm), but the external white
light-absorbing layer can generate the photocatalytic effect at or
near the surface of the device in response to the white light,
thereby providing ROS in the region of the infection.
In some embodiments (not shown), it is desirable to create a hole
or window in the reflective layer and additionally, for some
embodiments, the partially reflective layer, to allow access by the
fiber optic to the light port, for example at the proximal end of
the waveguide of the implants discussed above, and to increase the
light throughput to the waveguide. Because of this increased light
throughput, a thicker, more reflective layer (e.g., 80-90%
reflective) can be suitably used with more efficiency.
It is to be appreciated that other light-related components, such
as bifurcated fiber optic bundles and fluorescent or phosphorescent
chemical mediators, that are designed to manipulate light and allow
the light to reach remote surfaces of the device can also be used
to deliver light to the waveguide, and are also contemplated by the
present invention.
In some embodiments, the light source is a UV light source. The UV
light source is adapted to provide UV radiation to a UV-sensitive
photocatalytic surface in an amount effective to produce an amount
of ROS sufficient to reduce the local microbe concentration. In
some embodiments, the wavelength of the UV light is UVA light and
emits light having a wavelength in the range of 320 and less than
380 nm. In this range, for example, the UVA light effectively
irradiates conventional TiO.sub.2 and does not cause damage to DNA
as does UVC light.
In some embodiments, the UV light source has a spectral maximum in
the range of the UV and near-UV components of the solar spectrum.
For example, the light source can be provided with a spectral
maximum in the range of less than about 380 nm, and is some
embodiments between 300 nm and 380 nm. In some embodiments, the
light source has a spectral maximum of about 356 nm.
In some embodiments, UV or near UV light sources are used in
conjunction with semiconductor materials that exhibit
photocatalytic activity when irradiated by UV or near UV light. One
example of a semiconductor suitably used with UV light is
titania.
In other embodiments, the light source can be a white light source.
The white light source can be adapted to provide white light to the
photocatalytic surface in an amount effective to reduce the local
microbe concentration. For example, the light source can be adapted
to provide the wavelength of the white light is in the range of 380
nm-780 nm. In some embodiments, white light is used because it
effectively irradiates vanadium-doped TiO.sub.2 or nitrogen-doped
TiO.sub.2 to produce photocatalysis and does not cause damage to
DNA.
In some embodiments, using doped titania as the photocatalytic
surface, visible light having a maximum absorption wavelength of
between 400 nm and 650 nm is used. In some embodiments, using doped
titania as the photocatalytic surface, visible light having a
maximum absorption wavelength of between 450 nm and 600 nm is used.
In some embodiments, using doped titania as the photocatalytic
surface, visible light having a maximum absorption wavelength of
between 450 nm and 500 nm is used.
The present inventors have appreciated that, in some situations, it
may be possible to effectively irradiate an implanted device having
a photocatalytic layer, wherein the irradiation is transcutaneous.
It has been reported in the literature that the effective depth of
penetration of light through the skin is wavelength dependent and
is approximately as follows:
TABLE-US-00001 Depth of Wavelength Penetration 380 nm 1 mm 600 nm 4
mm 780 nm 10 mm
Accordingly, if the selected photocatalytic layer actives when
irradiated by, for example a 600 nm wavelength light, then an
implant comprising a photocatalytic layer can be implanted at a
depth of less than about 4 mm and transcutaneously irradiated to
effectively produce the desired photocatalytic reaction.
In some embodiments, an implant having a nitrogen-doped titania
layer is implanted beneath the skin at a depth of about 3 mm, and
the photocatalytic layer is irradiated with 600 nm light to produce
a photocatalytic reaction that provides the ROS sufficient to
destroy a biofilm located upon that photocatalytic surface.
In some embodiments, the light source is located external to the
patient. Providing an external light source simplifies the design
of the implant. In cases where irradiation occurs prior to the
operation and the implant is still outside the patient, the light
source may be a light box. In cases where irradiation occurs during
the operation and the patient's wound is open, the light source may
be a conventional light source, such as a flood light or the
operating room lights. In cases where irradiation occurs after the
operation and the patient's wound is closed, the light source can,
for example, transmit light through a fiber optic cable having a
proximal end connected to the light source and a distal end adapted
for entry into the patient and connection to the implant as has
been discussed herein.
According to some embodiments, the fiber optic cable used in
conjunction with an external light source is adapted to have the
strength and flexibility sufficient to navigate within the
patient's tissues. For example, the fiber optic cable can be
provided with a fine diameter. The proximal end of the fiber optic
is adapted for connection to the light source, while the distal end
of the fiber optic is adapted for connection to a waveguide or
lightport disposed at the implant. Activation of the light source
sends light from the light source through the fiber optic and into
the implant (such as to the wave guide component of the
implant).
According to some embodiments, some suitable fiber optic cable
materials include quartz and silica, which are commonly
available.
As shown above in FIG. 7, in some embodiments of the invention a
protective delivery needle 41 or catheter can be used in
conjunction with the fiber optic cable 103. The catheter has a long
bore adapted to house the fiber optic and functions to protect the
relatively thin fiber optic from undesired stresses encountered
during navigation to the site of infection. The catheter can also
serve as a protective shield that protects the surrounding tissue
from any undesired effects caused by light being transmitted
through the fiber optic.
According to some embodiments of the invention, so as to insure
against the spread of the infection by the catheter and/or fiber
optic cable, each of these components may be coated with a thin
layer 51,53 of a photocatalytic material, such as titania.
Irradiation of these thin layers by the light source can
effectively sterilize each of these components. Further description
of such a system is described supra.
In some embodiments, the light source is provided on the implant
and is adapted to be permanently implanted into the patient. One
advantage of such an implant comprising a light source is that when
a periprosthetic infection occurs post-operatively, there is no
need for further transcutaneous invasion of the patient. Rather,
the internally-disposed light source is activated by, for example,
a battery disposed on the implant or, for example, by a telemetry
signal. In some embodiments of the present invention comprising an
internal light source, the light source is provided by a bioMEMs
component. In some embodiments thereof, the internal light source
comprises a UV light source, and in some embodiments comprises an
AlGaN substrate. It has been reported by Stutzmann, Diamond and
Related Materials, 11 (2002) 886-891, that AlGaN may have future
application as a biosensor. Stutzman further conducted studies on
the biocompatibility of GaN, AlGaN and AlN, and found very little
interaction with living cell tissue, thereby suggesting the
biocompatibility of these materials. Accordingly, it is to be
appreciated that the light source may comprise any of these
materials.
In addition, in some embodiments, the bioMEMS light source may also
be adapted to act as a sensor of infection. In such embodiments,
the implant can function as an early detection system that can be
configured to warn the clinician of a growing infection and can be
used to treat the infection early.
In some embodiments, the light source is configured to produce
between about 0.1 watt and 100 watts of energy. It is believed that
light transmission in this energy range will be sufficient to
activate the photocatalytic surface on most implants. In some
embodiments, the light source is configured to produce an energy
intensity at the photocatalytic surface of between 0.1
watts/cm.sup.2 and 10 watts/cm.sup.2. In some embodiments, the
light source is configured to produce about 1 milliwatt/cm.sup.2.
This latter value has been reported by Ohko et al., JBMR (Appl
BioMat) 58: 97-101, 2001, to effectively irradiate a TiO.sub.2
surface in an amount sufficient to produce a photocatalytic effect.
It is to also to be appreciated that the light source can be
configured to produce light at power levels outside these ranges,
and is contemplated by the invention.
Since photocatalytic oxidation is generally believed to be a
relatively ambient-temperature process, the heat produced by both
the light source transmission and the desired oxidation reactions
are believed to be negligible. That is, the temperature of the
tissue surrounding the implant will not generally significantly
increase during activation of the PCO unit, and so the surrounding
tissue will not be thermally degraded by the therapies disclosed
herein.
Now referring to FIG. 11, there is provided an exemplary PCO unit
having an external light source 101. An externally based-control
device can comprise the light source 101 for providing light to the
implant device, such as to an endplate of an intervertebral motion
disc 201. The light generated by this source is transmitted via
fiber optic cable 103 through the patient's skin S to an
internally-based waveguide 21 though a light port 109 provided at
the implant 201. The light port is adapted to be in
light-communication with wave guide 21, to receive distal end 105
of the fiber optic and is disposed adjacent the outer surface 203
surface of the implant. A photocatalytic element 23 disposed
adjacent to the wave guide receives the light from the waveguide
and produces photocatalysis.
Now referring to FIG. 12, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIG. 11, and that for the sake of not be overly
duplicitous, the description of these components is not again
provided. FIG. 12 illustrates a second exemplary PCO unit having an
internal light source. Externally based-control device 222 has an
RF energy source 224 and an antenna 230 for transmitting signals to
an internally-based antenna 232 provided on the prosthesis. These
antennae 230, 232 may be electro-magnetically coupled to each
other. The internal antenna 232 sends electrical power through a
conductor 236 overlying an insulator 238 to a light emitting diode
(LED) 234 disposed internally on the implant in response to the
received signal transmitted by the external antenna 230. The light
generated by the LED is coupled to and propagated by the wave guide
21 to the photocatalytic layer 23.
In some embodiments, the prosthesis may further contain an internal
power source, such as a battery (not shown), which can be
controlled by an internal receiver that can receive a signal to
activate the battery, and the battery can be configured to have
sufficient energy stored therein to deliver electrical power to the
light source of the PCO unit sufficient to cause the desired
photocatalytic effect.
In some embodiments, the light generated by the internal PCO unit
is powered by a wireless telemetry receiver integrated onto or into
the prosthetic or implant itself. In the FIG. 12 embodiment, the
LED 234 may also comprise a radiofrequency-to-DC converter and
modulator (not illustrated). For such an arrangement, the
radiofrequency signals emitted by the antenna 230 can be picked up
by the antenna 232. These signals are then converted by the
receiver into electrical current to activate the light source of
the PCO unit.
In some embodiments, the telemetry devices can be conventional,
commercially-available components. For example, the
externally-based power control device 222 can be any conventional
transmitter, preferably capable of transmitting at least about 40
milliwatts of energy to the internally-based antenna 232. Examples
of such commercially available transmitters are available from
Microstrain, Inc. of Burlington, Vt. Likewise, the internally-based
power antenna can be any conventional antenna capable of receiving
and producing at least about 40 milliwatts of energy in response to
coupling with the externally-generated RF signal. Examples of such
commercially available antennae include those used in the
Microstrain Strinlink.TM. device. It is to be appreciated that
conventional transmitter-receiver telemetry is capable of
transmitting up to about 500 milliwatts of energy to the
internally-based antenna, which is also contemplated by the
invention.
In some embodiments, and now referring to FIG. 13, the implant
includes a light emitting diode (LED) 234 built upon a base portion
3 of the implant, along with components to achieve trans-dermal
activation and powering of the device. These components can
include, but are not limited to for example, RF coils 301, control
circuitry 303, a battery 305, and a capacitor (not illustrated).
Such a device could be capable of intermittent or sustained
activation from an external source of signal, without penetrating
the skin, thereby avoiding trauma to the patient and/or risk of
infection from skin-borne bacteria.
As discussed above, the accessory items used to power and control
the LED may be embedded within the implant. However, they could
also be located on the surface(s) of the implant, or at a site
adjacent to or near the implant, and in communication with the
implant, which are all contemplated by the invention.
In some embodiments, the telemetry devices of the implant can be
provided by vapor depositing a metallic material upon an
appropriate insulating substrate. For example, referring again to
FIG. 12, the internal antenna 232 can be suitably manufactured by
first creating an appropriate insulating substrate 238 upon an
implant surface and then CVD depositing a metallic layer in the
form of a coil upon the insulating surface.
In some embodiments, it may be desirable to locate the light
source, associated controller, power and telemetry components at a
location separate from the implant, and provide a light
communication device between the two sites. The light communication
device may include, for example, any of a fiber optic cable, a wave
guide, a hollow tube, a liquid filled tube, and a light pipe. Such
a configuration would allow the implant to be located deep within
the patient, or in or near critical organs or tissues, and yet have
the light source and associated components in a less sensitive
region. This configuration allows easier access to the
light/controller should the need arise for service or maintenance,
and also allows for more efficient transdermal energy transmission.
Moreover, by using a hollow tube with reflective internal surfaces
as the light transmission device, light and also therapeutic fluids
could be delivered to the implanted device. The light
source/controller implanted near the patient's skin could also be a
simple, hollow chamber made to facilitate the percutaneous access
as has been described above. Some advantages and benefits of this
system include: further removal from the deep site of the light
source/controller of the functional implant, thereby reducing risk
of contamination of the deeper site by percutaneous access; easier
precutaneous access to the light source/controller by being closer
to the skin surface and having a larger surface area or target to
access with the needle; a larger volume reservoir of the light
source/controller could hold more therapeutic fluid to provide a
longer duration of activity; and such a remote controller could
serve as a central reservoir to provide therapeutic fluids to
multiple implants throughout the body.
In some embodiments, the photocatalytic capabilities of the implant
device of the present invention may be supplemented with an adjunct
system for treating a periprosthetic infection. One such system
comprises a pharmaceutical delivery system. In some embodiments,
the pharmaceutical delivery system is a coating comprising a
pharmaceutical, wherein the coating is disposed upon a surface of
the implant. This coating acts as a sustained release device for
the pharmaceutical that insures a constant introduction of the
pharmaceutical into the surrounding tissue.
In some embodiments, an implant comprising the pharmaceutical
coating is disposed within a porous scaffold adapted to interface
with a bony surface. This embodiment not only places the
pharmaceutical at a location highly susceptible to infection, but
also insures that the physical integration between the implant and
the bony surface will not be compromised when the coating
eventually disappears.
In some embodiments, pharmaceutical delivery system comprises a
drug pump containing a pharmaceutical. The drug pump can be
activated either at the end of the surgery or afterward to provide
a constant introduction of the pharmaceutical into the surrounding
tissue.
In some embodiments, the pharmaceutical delivery system comprises
at least one channel created within or on the surface of an implant
for delivering the pharmaceutical to a plurality of locations about
the implant surface. According to some embodiments, the channel is
fully enclosed by the implant and defines an entry port (adapted
for receiving a needle) located upon a first surface of the implant
and at least one exit port opening onto a second surface of the
implant. It is to be appreciated that according to such
embodiments, when a plurality of channels and exit ports extend
from the same entry port, a pharmaceutical can be injected into the
entry port of the implant and carried through the channels to the
plurality of exit ports. With this arrangement, the pharmaceutical
can be spread over the surface adjacent the exit ports in an amount
effective to provide a beneficial effect. In some embodiments, the
channels can comprise porous material.
Now referring to FIG. 14, in some embodiments of the present
invention, there is provided an implant having a base material 3, a
porous photocatalytic intermediate layer 7, an outer reflective
(e.g., silver) coating layer 31, and a fluid delivery device 111
for delivering fluids to the implant. The device for delivering
fluids 111 can be the same structure used as a light port,
discussed herein, thereby providing the implant with two functions
in the same structure. According to such embodiments, the fluid
delivery device is capable of infusing a desired fluid over the
entire surface of the device. This can be accomplished by the use
of the porous layer 7 (e.g., a plasma sprayed titanium layer as is
commonly used on orthopedic implant). In some embodiments, a porous
channel 113 (shown by dotted lines) can be built into the porous
layer to provide a more even distribution of the fluid throughout
the porous layer. In some embodiments, the porous layer can also
function as the light waveguide and photocatalytic layer as has
been discussed supra.
It is to be appreciated that the porous nature of the intermediate
layer 7 provides for bony ingrowth, while the photocatalytic nature
of this layer provides for antimicrobial activity upon
post-surgical irradiation. In addition, the outer reflective
coating 31 layer provides both desirable reflection of light back
into the photocatalytic layer and immediate antimicrobial activity
without any further post-surgical intervention.
In some embodiments, the pharmaceutical is selected from the group
consisting of an antibiotic, a growth factor and an
anti-inflammatory. In such embodiments, the antibiotic can be
delivered to the adjacent tissue in an amount effective to prevent
a periprosthetic infection. Suitable antibiotics are desirably
delivered in conventional prophylactic concentrations. In such
embodiments, the growth factor can be delivered into the adjacent
tissue in an amount effective to enhance bony in-growth into the
porous layer, thereby securing attachment of the implant to the
adjacent bone. In such embodiments, the anti-inflammatory can be
delivered to the adjacent tissue in an amount effective to
antagonize pro-inflammatory cytokines, and thereby prevent bone
loss. Suitable anti-inflammatories include anti-TNF-.alpha.
compounds and anti-interleukin-1.mu.compounds. Specific desirable
compounds include (Remicade.TM.).
According to some embodiments, the pharmaceutical delivery system
comprises a silver halide coating. It is believed that the silver
component of this coating becomes ionized following dissolution.
Once ionized, it can enter the cellular membrane of adjacent
microbes and promote an intra-cellular reaction that produces
singlet oxygen. It is believed that the singlet oxygen so produced
has a lethal effect upon the invaded cell. In one embodiment
thereof, the silver halide coating can also be used as a reflective
coating adjacent a wave guide.
In some embodiments, hydrogen peroxide can be delivered through the
fluid delivery mechanisms discussed herein, to be present in the
vicinity of the photocatalytic layer. It has been reported in U.S.
Pat. No. 4,861,484 ("Lichtin") that hydrogen peroxide has a
significant synergistic effect upon the titania-based
photocatalysis. For example, Lichtin reports that the destruction
of certain organic compounds proceeds about 5-10 times as rapidly
when titania is irradiated in the presence of hydrogen peroxide (as
compared to its destruction rate when titania irradiated without
hydrogen peroxide). Accordingly, it is believed that the provision
of hydrogen peroxide with the present invention may enhance the
effectiveness of the desired photocatalytic activity.
In some embodiments, a photosensitizer can be delivered through the
fluid delivery mechanisms discussed herein, to be present in the
vicinity of the photocatalytic layer. It has been reported by
Wainright, J. Antimicrobial Chemotherapy, (1998) 42, 13-28, that
local irradiation of photosensitizers (such as methylene blue)
should be considered as a mechanism for treating local infection
due to their ability to produce singlet oxygen. Accordingly, it is
believed that the additional provision of photosensitizers with the
present invention may enhance the effectiveness of the desired
photocatalytic activity. In some embodiments, the photosensitizer
is selected from the group consisting of phenothiazinium type,
phenazine type, acridine type, cyanine type, porphyrin type,
phthalocyanine type, psoralen type, and perylenequinonoid type.
In some embodiments, a luminescent compound can be delivered
through the fluid delivery mechanisms discussed herein, to be
present in the vicinity of the photocatalytic layer. It is known
that certain luminescent materials such as luminol can react with
other reactants to produce light. Luminol is of particular interest
in that the light produced from its reactions is about 424 nm. This
424 nm light should be effective to produce the excitation of some
of the doped titania discussed above. Accordingly, it may be
possible to produce the required light around an infected implant
without the need for an invasive fiber optic cable. Accordingly, it
is believed that the provision of providing a luminescent compound
in accordance with some embodiments of the present invention may
enhance the effectiveness of the desired photocatalytic activity.
In some embodiments, the photosensitizer is selected from the group
consisting of bioluminescent and chemiluminescent compounds.
Now referring to FIG. 15, in some embodiments, the PCO unit is
provided upon a hip prosthetic. In some embodiments, a
photocatalytic layer 1501 is provided upon a surface 1503 of the
base material 1502 located upon the femoral stem of the implant. As
shown in FIG. 15, the photocatalytic layer is preferably encased in
a reflective layer 1505. Preferably, each of these layers is porous
and is suitable as a porous scaffold for bony ingrowth. In other
embodiments, the photocatalytic layer is provided upon a surface
located upon the femoral head (not shown) of the implant. In some
embodiments, the photocatalytic layer is provided upon a surface
located upon the acetabular cup (not shown) of the implant. In some
embodiments, the prosthetic further has a light port (not shown) to
facilitate illumination of the photocatalytic surface.
Now referring to FIG. 16, in some embodiments, the PCO unit is
provided upon a knee prosthetic 1601 such as illustrated in FIG.
16. In some embodiments, thereof, a photocatalytic layer 1603 is
provided upon a surface 1602 of a base material 1604, and is
substantially encased in a reflective layer 1605. According to some
embodiments, each of these layers is porous, is suitable as a
porous scaffold for bony ingrowth, and is provided upon a surface
adapted to contact bone. According to some embodiments, the
prosthetic further has a light port (not shown) to facilitate
illumination of the photocatalytic surface.
In some embodiments, a bone screw is provided with a photocatalytic
surface. For example, now referring to FIG. 17, in some embodiments
a bone screw 121 comprises a body portion 123 made from a light
transmissible material (such as single crystal sapphire), an outer
surface 125 at least a portion of which is threaded 126, a proximal
portion 127, a distal portion 129 containing a narrow head portion
131, a photocatalytic surface 133 disposed upon the outer surface
of the screw, a light source 135 (such as an LED) disposed upon the
proximal portion of the screw, and an antenna 137 in electrical
connection with the light source. It is to be appreciated that in
some embodiments of the bone screw, the LED and antenna can be
replaced with a light port, and the light source can be externally
based.
In some embodiments, the PCO unit is provided upon a spinal
prosthetic. In some embodiments, thereof, it is provided upon a
motion disc. In some embodiments it is provided upon a scoliosis
correction system. In some embodiments it is provided upon an
intervertebral fusion device.
For example, now referring to FIG. 18, in some embodiments, an
intervertebral fusion device 1801 is provided with the
photocatalytic surface 1803. In some embodiments, a photocatalytic
layer 1803 is a composite layer comprising a wave guide, as has
been discussed herein, and the photocatalytic material. The
photocatalytic layer 1803 is provided upon at least one of upper
and lower bearing surfaces 1805 of the fusion device. In some
embodiments, thereof, the photocatalytic layer 1803 is
substantially encased in a reflective layer 1807. According to some
embodiments, each of these layers is porous and is suitable as a
porous scaffold for bony ingrowth. According to some embodiments,
the prosthetic may also have a light port 1809 to facilitate
illumination of the photocatalytic surface. In other embodiments,
the photocatalytic surface is provided upon at least one internal
surfaces of the fusion device (not illustrated).
Now referring to FIG. 19, the PCO unit can be provided upon an
intervertebral motion disc 501. According to some embodiments, the
motion disc is selected from the group consisting of a cushion disc
and an articulating disc. In some embodiments, the articulating
disc 501 comprises a first prosthetic vertebral endplate 511
comprising an outer surface 513 adapted to mate with a first
vertebral body VB1, and an inner surface comprising a first
articulation surface 515 suitable for supporting articulation
motion. The articulating disc also comprises a second prosthetic
vertebral endplate 521 comprising an outer surface 523 adapted to
mate with a second vertebral body VB2, and an inner surface 524
comprising a second articulation surface 525 suitable for
supporting articulation motion. As shown in FIG. 19, some
embodiments comprise a wave guide 21 that overlies outer surface
523, and a photocatalytic layer 23 overlies the wave guide. A light
port or an LED (neither shown) may be placed in light communication
with the wave guide, as has been discussed herein.
In some embodiments, the motion disc is a two-piece design (wherein
the articulation surfaces of the prosthetic endplates are adapted
to form an articulation interface). In others, the motion disc is a
three-piece design further including a core (wherein opposed
articulation surfaces of the core are adapted to form two
articulation interfaces with the corresponding articulation
surfaces of the prosthetic endplates).
It is known that scoliosis correction systems are associated with a
higher than normal rates of infection. Therefore, in some
embodiments, at least one component of the PCO unit is provided
upon a spinal deformity unit. In some cases, the bone screw of the
spinal deformity unit is provided with the photocatalytic surface
as has been discussed herein, for example, with respect to FIG. 17.
In some embodiments, a rod component of the spinal deformity unit
is provided with the photocatalytic surface.
For example, now referring to FIG. 20, a cross-connector component
2001 of the spinal deformity unit is provided with a photocatalytic
layer 2003. In the illustrated embodiment, nuts 2008 hold the
cross-connector to the screws 2009. In some embodiments, the
photocatalytic layer 2003 of FIG. 20 is a composite layer
comprising the wave guide and the photocatalytic material as
discussed herein. The photocatalytic layer 2003 is provided upon at
least one of the inner 2004 and outer 2005 surfaces of the base
material of the cross-connector that faces the tissue. In some
embodiments, thereof, the photocatalytic layer 2003 is
substantially encased in a reflective layer 2007. According to some
embodiments, each of these layers is porous and is suitable as a
porous scaffold for bony ingrowth. According to some embodiments,
the prosthetic further has a light port 1809 (See FIG. 18) to
facilitate illumination of the photocatalytic surface.
Now referring to FIG. 21, it is to be appreciated that like
reference numerals used herein but not specifically described,
correspond to like components, layers, previously described herein,
such as with respect to FIGS. 12 and 19, and that for the sake of
not be overly duplicitous, the description of these components is
not again provided. In some embodiments, the PCO unit can be
located upon a bone in-growth surface such as surface 550 of the
prosthetic implant. In this embodiment, the photocatalytic layer 23
is in light communication with the LED 234 via wave guide 21,
thereby obviating depth of UV penetration concerns as has been
discussed herein. This embodiment also has an advantage of
providing all of the PCO components on the same surface, thereby
allowing for ease of manufacturing by a CVD process. Moreover, when
the PCO unit is so situated, the activated species produced thereby
quickly engage any bacteria present at the point of the wound.
Now referring to FIG. 22, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-21, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. In some embodiments, the LED 234 can be located
upon an inner surface 524 of the prosthetic implant, and the
photocatalytic layer 23 is in light communication with the LED 234
via wave guide 21. This embodiment has a mechanical advantage in
that when the PCO unit is so situated, it is likely subjected to
less stresses and so it electrical connections are less likely to
fail.
Now referring to FIG. 23, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-22, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. In some embodiments, the LED 234 can be located
upon a peripheral rim surface 552 of the prosthetic implant. This
embodiment has an advantage that, when the PCO unit is so situated,
and the infection occurs at a point of internal sutring, the
activated species produced by the quickly engage peripheral
bacteria located in that sutre.
Now referring to FIG. 24, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-23, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. In some embodiments, the LED 234 of the PCO unit
can be located upon a bone in-growth surface 550 of the prosthetic
implant, while the antenna 232 can be located upon another surface
such as the inner surface 524. This embodiment has an advantage
that the PCO unit is in proximity to the bacteria present at the
point of the wound, and the remote placement of the antenna does
not interfere with the UV penetration of the bone-prosthetic
interface.
Now referring to FIG. 25, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-24, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. In some embodiments, the photocatalytic layer 5
can be produced by oxidizing a titanium-containing surface of a Ti
alloy implant. The oxidation of the surface of a titanium alloy
implant can be carried out by the teachings of Trepanier, discussed
supra. One advantage of such embodiment is that the photocatalytic
layer spreads across substantially the entire lower surface of the
implant, and is situated precisely at the often-problematic
bone-implant interface 550.
Now referring to FIG. 26 it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-25, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. In some embodiments, the photocatalytic layer 27
comprises porosity 30 to provide a porous scaffold suitable for
bone growth. For example, a porous scaffold of titania film can be
manufactured as described above. Some advantages of such embodiment
of an implant device are that the porous TiO.sub.2 portion of the
device provides two functions. First, the porous nature of this
scaffold allows for bony ingrowth. Second, the UV sensitive nature
of the TiO.sub.2 material allows its irradiation by LED 234 to
produce ROS capable of disinfecting the entire porous scaffold.
Now referring to FIG. 27, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-26, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. According to this embodiment, there is provided
a device of the present invention in which the LED 234 is centrally
located on the outer surface of the implant, for example, at the
bone-implant interface 550 and is surrounded by a UV transmissible
material forming a wave guide 21. Some exemplary suitable
UV-transmissible materials include alumina, silica and sapphire. A
porous scaffold comprising TiO2 overlays the UV-transmissible
peripheral layer and forms the photocatalytic layer 23. One
advantage of this embodiment of the implant device is that the UV
transmissible material acts as a wave guide, so that the UV light
generated from the LED can spread laterally across the surface of
the implant and thereby irradiate the titania in the porous
scaffold over the entire surface.
Now referring to FIG. 28, it is to be appreciated that reference
numerals used herein but not specifically described, correspond to
like components, layers, previously described herein, such as with
respect to FIGS. 12, and 19-27, and that for the sake of not be
overly duplicitous, the description of these components is not
again provided. In addition, it is to be appreciated that for the
sake of simplicity, like parts have not all been labeled with
reference numbers. According to this embodiment, there is provided
a device of the present invention wherein the porous scaffold
comprises both a first wave guide 21 and a composite layer 27
comprising the semiconductor material 29 and a light-transmissible
(for example, UV-transmissible) material 25. It is to be
appreciated that this embodiment as well as each of these
embodiments can be provided so as to have the properties and
advantages that have been discussed herein with respect to other
embodiments comprising these layers and components.
In other embodiments, the LED and antenna components disclosed with
respect to the above described embodiments, can be replaced by a
wave guide light receiving port. With such an arrangement, an
externally-disposed fiber optic can be inserted into the patient,
connected to the wave guide port, and activated as has been
discussed supra.
It is to be appreciated that in some instances, the implant can be
subject to therapeutic photocatalytic treatment prior to its
implantation. Pre-implantation treatment is a preventative measure
that can provide the surgeon with extra assurance that the implant
is sterile when it enters the body. For example, providing a
pre-implantation photocatalysis can also reduce the risk that
transmissible diseases such as mad cow disease and AIDS become
problematic.
In some pre-implantation embodiments thereof, an implant can be
placed in an aqueous slurry of titania particles and photoenergy
can be applied to provide the slurry to produce the photocatalysis.
The ROS produced by the photocatalysis will oxidize not only any
bacteria attached to the implant, but also problematic spores. It
has been reported by Wolfrum, Environ. Sci. Tech., 2002, 36,
3412-19 that a titania-based reactor exposed to about 10
mW/cm.sup.2 of 365 nm light is sufficient to kill A. niger
spores.
It is to be appreciated that photocatalysis can also be provided
upon the implant intra-operatively (i.e., during the surgery). For
example, just prior to closing the patient, the surgeon can use a
fiber optic to irradiate the photocatalyzable surface of the
implant, thereby insuring that any bacteria that became attached to
the implant during the surgery will be rendered ineffective. It is
believed that a substantial percentage of problematic PPIs arise
from infection occurring at the interface of the patient's bone and
the implant, and that such an arrangement can be used to mitigate
such PPIs.
Therefore, in some embodiments, the implant of the present
invention is implanted into the patient and the PCO unit is then
activated during the surgery. In some embodiments, the PCO unit
activation occurs immediately prior to closing up the patient.
In some embodiments, the PCO unit activation occurs immediately
after closing up the patient. For example, the patient can be
closed with the fiber optic still attached to the wave guide port.
The surgeon then uses the fiber optic to irradiate the
photocatalyzable surface of the implant, thereby insuring that any
bacteria that became attached to the implant during the surgery
will be rendered ineffective. After irradiation, the fiber optic is
drawn from the patient.
In some embodiments, the herein described PCO procedures can be
configured to effectively act upon the target bacteria colony to
eliminate at least 50% of the colony, preferably at least 90%, and
more preferably at least 99%. In some embodiments, the ROS
generated by the PCO unit are provided so as to be present in the
reaction zone is an amount effective to sterilize the reaction
zone. The sterilization of the reaction zone means that spores in
addition to bacteria are killed. In some embodiments, the PCO
procedure can be configured to effectively essentially completely
oxidize the target bacteria to carbon dioxide and water.
In some embodiments, the ROS generated by the PCO unit can be
provided in the reaction zone is an amount effective to disinfect
the reaction zone. Typically bacteria that are considered to be
prone to photocatalysis include, but are not limited to,
staphylococcus epidermis. Microbes involved in mad cow disease and
AIDS are also contemplated to be within the scope of the system and
method for treating infections of the present invention.
Staphylococcus epidermis is thought to be introduced into the
patient through the normal flora of the skin. As has been discussed
herein, these types of bacteria tend to form a biofilm on the
surface of the implant, which can be eliminated by the herein
described methods and apparatus of the invention.
It is to be appreciated that although the above discussion has
focused upon providing photocatalytic devices for treating or
preventing infection, the present inventors believe that
photocatalytic implants may also be used to treat other
non-infection conditions. For example, a cardiovascular stent may
be designed to possess a photocatalytic unit that photooxidizes
cells within inflamed intimal tissue involved in the local
inflammatory process caused by deployment of a stent, thereby
preventing restenosis. In another example, a tubular device housing
a needle may be adapted for peripheral photooxidation of the cells
involved in the local inflammation caused by invasion from the
needle, thereby preventing FOP. In another example, a device may be
adapted for peripheral photooxidation of the cells and particles
involved in the local inflammation caused by wear debris involving
small UHMWPE particles, thereby preventing osteolysis.
Having thus described several aspects of at least one embodiment of
this invention, it is to be appreciated various alterations,
modifications, and improvements will readily occur to those skilled
in the art. Such alterations, modifications, and improvements are
intended to be part of this disclosure, and are intended to be
within the spirit and scope of some embodiments of the present
invention. Accordingly, the foregoing description and drawings are
by way of example only.
* * * * *